The goals of the proposed research are to study and characterize the properties of and interactions among exchange of CO2 and O2 in lung and tissue capillary beds, bicarbonate/chloride exchange across cell membranes, hydration-dehydration reactions of CO2 and H2CO3 in tissue, plasma, and erythrocytes, and pH disequilibrium phenomena. This integrated information on the organ, cellular and molecular levels will be useful for deeper understanding of gas exchange and acid-base homeostasis in healthy individuals and in those with disease, and for further insight into the effects of these interactions on normal physiological processes. Our long-range objective is to contribute to the development of improved therapeutic options for the management of gas exchange and acid-base abnormalities in humans with lung, blood, and other diseases. pH disequilibrium studies will be performed in humans and animals using our previously stopped-flow pH electrode apparatus. These studies will be performed in normal controls and during clinical carbonic anhydrase inhibition. The effects of slow pH changes on physiological processes will be determined. We will study the localization of carbonic anhydrase in tissue, and its fate when added to plasma in vivo. Using our stopped-flow rapid reaction apparatus, bicarbonate/chloride exchange across the red cell membrane will be studied under a number of experimental conditions, including changes of temperature and pH. The influence of drugs, disease, and membrane alterations will be determined. The role of bicarbonate/chloride exchange in the regulation of intracellular tissue pH will be investigated. Perhaps most important, the interactions between bicarbonate/chloride kinetics across the red cell membrane and gas exchange in vivo will be determined. These studies will be performed theoretically, and on in vitro and in vivo preparations. The diffusing capacity of the alveolar-capillary membrane for CO2 will also be measured. These latter studies promise to yield insight into abnormalities of gas exchange in humans in vivo, and may lead to new therapeutic maneuvers for the management of these disorders.